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N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.

Pusceddu MM, El Aidy S, Crispie F, O'Sullivan O, Cotter P, Stanton C, Kelly P, Cryan JF, Dinan TG - PLoS ONE (2015)

Bottom Line: Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored.In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals.This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.

ABSTRACT

Background: Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored.

Methods and results: Here, we show that long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut-microbiota composition of maternally separated (MS) female rats. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS, and to a lesser extent the NS rats, and was associated with attenuation of the corticosterone response to acute stress.

Conclusions: In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals. This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.

No MeSH data available.


Related in: MedlinePlus

Correlation between percentage abundance of Akkermansia and Rikenella and corticosterone (CORT) plasma levels.Regression analysis revealed (A) negative correlation between low CORT levels in MS-saline group and low abundance of Akkermansia and (B) positive correlation between low CORT levels in MS-saline group and low abundance of Rikenella.
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pone.0139721.g003: Correlation between percentage abundance of Akkermansia and Rikenella and corticosterone (CORT) plasma levels.Regression analysis revealed (A) negative correlation between low CORT levels in MS-saline group and low abundance of Akkermansia and (B) positive correlation between low CORT levels in MS-saline group and low abundance of Rikenella.

Mentions: Recently, we showed that stress-induced corticosterone levels were reduced in MS group compared to the respective controls when exposed to acute stress [25]. In order to investigate a possible correlation between the altered microbiota in the gut of MS-saline group and the HPA, regression analysis was performed between corticosterone levels and the gut microbiota of MS and NS groups. Interestingly, a negative correlation with Akkermansia (R = 0.4097, P = 0.0019) and positive correlation with Rikenella (R = 0.4481, P = 6e-04) was observed (Fig 3). While Rikenella was reported to be associated with reduced risk of colitis [38](Couturier-Maillard, J Clin Invest. 2013 Feb 1; 123(2): 700–711), Akkermansia has been previously shown to exacerbate gut inflammation in mice [34, 35]. Thus, we consider that the observed high Akkermansia abundance in MS rats may contribute to elevated levels of inflammation, which in turn may activate the HPA as recently shown [25]. In view of that, persistent activation of HPA may eventually lead to end organ burnout and consequent lower CORT release. Accordingly, HPA hypoactivity has been previously reported in other animal models of stress [39–41].


N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.

Pusceddu MM, El Aidy S, Crispie F, O'Sullivan O, Cotter P, Stanton C, Kelly P, Cryan JF, Dinan TG - PLoS ONE (2015)

Correlation between percentage abundance of Akkermansia and Rikenella and corticosterone (CORT) plasma levels.Regression analysis revealed (A) negative correlation between low CORT levels in MS-saline group and low abundance of Akkermansia and (B) positive correlation between low CORT levels in MS-saline group and low abundance of Rikenella.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591340&req=5

pone.0139721.g003: Correlation between percentage abundance of Akkermansia and Rikenella and corticosterone (CORT) plasma levels.Regression analysis revealed (A) negative correlation between low CORT levels in MS-saline group and low abundance of Akkermansia and (B) positive correlation between low CORT levels in MS-saline group and low abundance of Rikenella.
Mentions: Recently, we showed that stress-induced corticosterone levels were reduced in MS group compared to the respective controls when exposed to acute stress [25]. In order to investigate a possible correlation between the altered microbiota in the gut of MS-saline group and the HPA, regression analysis was performed between corticosterone levels and the gut microbiota of MS and NS groups. Interestingly, a negative correlation with Akkermansia (R = 0.4097, P = 0.0019) and positive correlation with Rikenella (R = 0.4481, P = 6e-04) was observed (Fig 3). While Rikenella was reported to be associated with reduced risk of colitis [38](Couturier-Maillard, J Clin Invest. 2013 Feb 1; 123(2): 700–711), Akkermansia has been previously shown to exacerbate gut inflammation in mice [34, 35]. Thus, we consider that the observed high Akkermansia abundance in MS rats may contribute to elevated levels of inflammation, which in turn may activate the HPA as recently shown [25]. In view of that, persistent activation of HPA may eventually lead to end organ burnout and consequent lower CORT release. Accordingly, HPA hypoactivity has been previously reported in other animal models of stress [39–41].

Bottom Line: Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored.In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals.This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.

ABSTRACT

Background: Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored.

Methods and results: Here, we show that long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut-microbiota composition of maternally separated (MS) female rats. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS, and to a lesser extent the NS rats, and was associated with attenuation of the corticosterone response to acute stress.

Conclusions: In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals. This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.

No MeSH data available.


Related in: MedlinePlus